DESCRIPTION (provided by investigator): Adolescents and young women have the highest rates of cervical HPV, including infection with the HPV types causing significant morbidity and mortality. Introduction of the FDA-approved quadrivalent vaccine (Gardasil(R), Merck & Co.) targeting HPV16 and HPV18 (high-risk [HR] types present in >65% of cervical cancers), as well as HPV6 and 11 (associated with most genital warts), has the potential to reduce the burden of genital HPV and disease. HPV vaccine clinical trials focused exclusively on low-risk women with limited numbers of sexual partners who were highly compliant with the vaccine schedule; these females were not representative of those most at risk to suffer from HPV-related disease. In fact, Hispanic and African-American women have the highest and second highest incidence rates of cervical cancer in the U.S., respectively, and high mortality rates from cervical cancer. In addition, the associations of HPV-related anal and/or oropharyngeal lesions are an important public health concern, yet few vaccine studies in women have evaluated HPV at these sites. Subsequent to the approval and release of GARDASIL, we initiated a prospective cohort study of sexually- active, inner-city, minority adolescent women attending the Mount Sinai Adolescent Health Center (MSAHC), the largest comprehensive adolescent primary care facility in the U.S. To date, this project has enrolled more than 750 sexually active teens between the ages of 12-19. Prevalent HPV infection at enrollment was detected in 54% of cervical, 42% of anal and 20% of oral specimens, with vaccine types (HPV 6/11, 16 & 18) present in 7%, 6% and 1% of adolescents, respectively. Adolescents who had three doses were at significantly reduced risk of HPV vaccine types in the cervix compared to those who had no vaccination. With respect to extracervical sites, non-significant reductions were observed for HR-HPV vaccine types in the anal and oral cavities when comparing fully vaccinated to non-vaccinated adolescents. There was considerable incident (4.2 per 100 person years) detection of cervical HPV 16/18 infection not present at enrollment despite vaccination; this observed rate is substantially above that reported in the efficacy trials. We propose to address the health disparities of HPV in minority young women by continuing our cohort study of high-risk adolescent females participating in an HPV immunization program at MSAHC. We propose to extend the prospective follow-up (with repeat visits every 6 months) to evaluate the long-term burden of infection and to increase sample size to just over 1,400 subjects to improve statistical power. The increased sample size and longer follow-up will allow us to determine risk factors for break-through HPV infections, as well as integrate a new aim to evaluate psychosocial elements of adolescent development and high-risk behaviors in teens. Data obtained from this study will be essential to understanding the 'real-world' impact of HPV vaccination in this group not studied in the vaccine trials and will provide the biological underpinnings for future HPV and cervical cancer screening practices, as well as estimating the potential impact of vaccine on anal and/or oropharyngeal HPV infections.